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Biomedical subjects

Mostafa M Fraig

Publications and source records attributed to Mostafa M Fraig.

5 recordsLinked to original sources
PubMed2006

Iris-cyst-simulating luxated lens.

A 2-month-old child was referred to our clinic for evaluation and management of a luxated lens. Under general anesthesia, an irregularly shaped iris was observed with the presence of a large iris cyst in the anterior chamber. Sector iridectomy with excision of the cyst was performed. Histopathologic examination confirmed the diagnosis of a stromal cyst of the iris. At the 3-year follow-up, there was no evidence of recurrence of the iris cyst or of a secondary cataract. This case report provides evidence that although a primary cyst of the iris stroma is uncommon, it should be considered in the differential diagnosis for an apparent lens luxation.

Cysts↗
PubMed2005

CaSm-mediated cellular transformation is associated with altered gene expression and messenger RNA stability.

CaSm (cancer-associated Sm-like) was originally identified based on elevated expression in pancreatic cancer and in several cancer-derived cell lines. CaSm encodes a 133 amino acid protein that contains two Sm motifs found in the common small nuclear RNA proteins and the LSm (like-Sm) family of proteins. Compared with normal human prostate tissue and primary prostate epithelial cells, some primary prostate tumors and prostate cancer-derived cell lines have elevated CaSm expression. Expression of antisense CaSm RNA in DU145 cells results in reduced CaSm protein levels and less transformed phenotype, measured by anchorage-independent growth in vitro and tumor formation in severe combined immunodeficient mice in vivo. Additional data shows that adenoviral delivery of antisense CaSm inhibits the growth of prostate cancer cell lines by altering cell cycle progression, and is associated with reduced expression of cyclin B1 and CDK1 proteins. Consistent with failure of antisense-treated cells to enter mitosis, microarray analysis identified altered expression of NEK2 and nucleophosmin/B23. Although the mechanisms by which CaSm contributes to neoplastic transformation and cellular proliferation are unknown, it has been shown that the yeast homologue (spb8/LSm1) of CaSm is required for 5' to 3' degradation of specific mRNAs. We provide data consistent with a similar role for CaSm in human cells, supporting the hypothesis that elevated CaSm expression observed in cancer leads to destabilization of multiple gene transcripts, contributing to the mutator phenotype of cancer cells.

Adenoviridae↗
PubMed2003

Pdef expression in human breast cancer is correlated with invasive potential and altered gene expression.

Ets transcription factors control multiple biological processes, including cell proliferation, differentiation, apoptosis, angiogenesis, transformation, and invasion. Pdef is an Ets transcription factor originally identified in prostate tissue. We demonstrate that human Pdef is expressed at high levels primarily in tissues with high epithelial cell content, including prostate, colon, and breast. We also determined that Pdef protein is reduced in human invasive breast cancer and is absent in invasive breast cancer cell lines. We next assessed the functional consequences of these observations. Significantly, expression of Pdef in breast cancer cells leads to inhibition of invasion, migration, and growth. Expression of Pdef also results in the down-regulation of urokinase-type plasminogen activator and activation of the promoter of the tumor suppressor gene, MASPIN: Growth-suppressive effects of Pdef expression are mediated in part by a G(0)-G(1) cell cycle arrest associated with elevated p21 levels. Collectively, these results indicate that Pdef loss may alter the expression of genes controlling progression to invasive breast cancer.

Breast Neoplasms↗
PubMed2003

Alterations in PMS2, MSH2 and MLH1 expression in human prostate cancer.

DNA mismatch repair (MMR) is involved in the post-replication correction of errors due to misincorporated nucleotides or DNA slippage during DNA synthesis. We previously reported the reduction or loss of MMR protein expression in human prostate cancer cell lines and some primary tumors. In the present report, we further demonstrate the involvement of defects of MMR in the pathogenesis of prostate cancer. Immunohistochemical analysis of 39 formalin-fixed, paraffin-embedded human prostate tumors, showed reduction or absence of MMR protein expression (MLH1, MSH2, PMS2) in the epithelium of prostate tumor foci compared to normal adjacent prostate tissue. The reduction or absence of the PMS2 and MSH2 (but not MLH1) protein was correlated to the differentiation of the tumor. Poorly differentiated tumors showed greater loss of these two proteins than the well differentiated tumors (P<0.05). We previously reported that microsatellite instability was detectable by a beta-galactosidase restoration mutation assay in the prostate cancer cell lines DU145, PC3, LNCaP, p67SV40T, M2182, and M12. In this study, we detected the insertion or deletion of one nucleotide in the mononucleotide repeats located within the coding regions of BAX gene in DU145, and TGFbetaRII in M12 cells. In addition, we used an in vitro model of defective MMR to demonstrate that microsatellite instability can be induced in an otherwise stable cancer cell line by transfection with a dominant negative fragment of PMS2. These results suggest that defects in MMR may result in MSI in the secondary genes in prostate cancer. From these results, we conclude that loss of MMR function can produce MSI and target some secondary genes containing microsatellites in their coding regions. These series of events may play important roles in the development of human prostate cancer.

Adaptor Proteins, Signal Transducing↗